The direct assessment of cellular membrane function has been enhanced by the measurement of resting transmembrane potentials during hemorrhagic shock. The use of single muscle cell action potentials offers further evidence for intracellular changes in response to hemorrhagic shock. When combined with direct analysis of muscle, water and electrolyte composition, extracellular (ECW) and intracellular (ICW) partition during shock and recovery can be further quantitated. It is the purpose of this proposal to extend these techniques to study calcium flux in striated skeletal muscle and the myocardium during hemorrhagic and septic shock. In addition, the effect of pharmacologic agents on septic shock will be determined by measuring transmembrane potentials. This will allow documentation of specific defects in ion and water flux during septic shock resuscitation at the cellular level. Measurements of extravascular lung water (EVLW) in hemorrhagic and septic shock using both a double indicator technique (thermodye) and a standard gravimetric analysis will be extended. Comparisons will be made with different resuscitative regimens and their effect on pulmonary vascular permeability and microvascular forces. A bioassay is in a state of development based on the Langer rabbit septal preparation. This preparation will be used to isolate the shock permeability factors(s). In addition the preparation will be utilized to demonstrate the effect of shock plasma, live E. coli and endotoxin on the myocardium.